Sangamo Therapeutics, Inc. announced preclinical data from its proprietary adeno-associated virus (AAV) capsid variant, STAC-BBB, that demonstrated robust penetration of the blood-brain barrier (BBB) and strong transgene expression throughout the central nervous system (CNS) of NHPs when administered intravenously at clinically-relevant doses, outperforming results obtained by Sangamo for other known neurotropic capsid variants evaluated in the study. Importantly, potent repression of target genes was observed in brain cells expressing the zinc finger cargo, indicating that STAC-BBB could enable development of genomic medicines to potentially treat a wide range of neurological diseases. Sangamo intends to use the novel STAC-BBB capsid in its wholly owned prion disease and tauopathy programs. In addition, STAC-BBB could potentially unlock multiple neurology epigenetic regulation programs that were paused by Sangamo pending the identification of a suitable capsid, including programs previously in development under Sangamo?s former collaboration agreements with Biogen and Novartis.

Sangamo is exploring avenues to resume development of these programs internally, subject to receipt of adequate funding, or with new potential collaborators. Summary of STAC-BBB Preclinical Data In NHP studies when administered intravenously at clinically relevant doses, STAC-BBB demonstrated its potential to be a leading neurotropic capsid. Highlights include: Broad brain coverage.

Robust penetration of the BBB and widespread transgene expression throughout the brain, including key regions integral to human neurological diseases such as Alzheimer?s disease, Parkinson?s disease, Amyotrophic Lateral Sclerosis (ALS), Huntington?s disease and prion disease. Industry-leading brain tropism. Exhibited 700-fold higher transgene expression in neurons compared to the benchmark capsid AAV9 and outperformed all other known published neurotropic capsid variants evaluated in the study.

Widespread neuronal transduction across all animals. STAC-BBB mediatedrobust expression of zinc finger cargo in neurons, the key cell type to target for treatment of neurological diseases. Moreover, results were dose-dependent and consistent across all NHPs in the study.

Potent and widespread repression of target genes. Capsid-enabled delivery of zinc finger payloads resulted in the repression of prion and tau genes across key brain regions, demonstrating the potential for modification of disease progression in prion disease and various tauopathies. Visualization of gene expression in individual brain cells by RNAscope revealed highly potent repression of tau in neurons expressing the zinc finger cargo across multiple brain regions.

Desired de-targeting of the liver and other peripheral organs. Capsid biodistribution was shown to be enriched in the CNS and de-targeted from the liver, dorsal root ganglia (DRG) and other peripheral organs. This biodistribution profile demonstrated by STAC-BBB is optimal for an AAV-based treatment of neurological diseases.

Favorable safety profile. STAC-BBB was well tolerated in NHPs, with no notable treatment related pathological findings in brain, spinal cord or peripheral tissues. Manufacturable using standard processes and at scale.

Company believe STAC-BBB is manufacturable at commercial scale using standard cell culture and purification processes, is soluble using known excipients, and can be characterized using available analytics. Sangamo expects to file an IND submission for its Nav1.7 program addressing chronic neuropathic pain, which leverages an intrathecally administered capsid, in the fourth quarter of 2024, and a CTA submission for its prion disease program, which is expected to leverage the STAC-BBB capsid, in the fourth quarter of 2025, each subject to additional funding. Sangamo also intends to resume development of its tau program leveraging the STAC-BBB capsid, with an IND submission expected as early as the fourth quarter of 2025.